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Biomedical subjects

R Osborne

Publications and source records attributed to R Osborne.

At least 91 records · Page 5Linked to original sources
PubMed1985

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) enhances terminal differentiation of cultured human epidermal cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and isosteric halogenated analogs produce a spectrum of pathologic changes in the epidermis of humans. In this study, the actions of TCDD on cultured human epidermal cells were characterized to determine whether these cells are an appropriate in vitro model to examine the mechanisms of TCDD toxicity to human skin. The differential staining properties of TCDD-treated cultures indicated that TCDD decreased basal cell numbers and increased the degree of keratinization. Histologic examination of cross-sections of the cultures confirmed a loss of small nucleated cells and increased cell layering in response to TCDD. TCDD produced no change in total cell number or cell protein, but decreased the number of small (basal) cells and DNA synthesis. TCDD increased the number of cells containing spontaneous envelopes, as well as the number of envelope-competent cells. The quantitative changes observed in these parameters were consistent with a TCDD-induced commitment of proliferating cells to terminal differentiation. TCDD also decreased epidermal growth factor (EGF) specific binding. Maximal changes in EGF binding occurred after 4 days, and in small cell number after 5 days. The decreases in EGF binding and small cell number were stereospecific and concentration dependent (EC50, 1 to 2 nM), implicating the human Ah receptor in mediating these responses to TCDD. These data indicate that TCDD treatment produces hyperkeratinization in cultured human epidermal cells. It is proposed that TCDD acts on epidermal basal cells to enhance terminal differentiation through mechanisms regulated at least in part by the Ah receptor.

Cell Differentiation↗
PubMed1985

Actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human epidermal keratinocytes in culture.

In humans, the skin is a particularly sensitive target for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and certain halogenated analogs. Reported lesions include a thickening of the epidermis (acanthosis), hyperkeratosis, and squamous metaplasia of the epithelial lining of the sebaceous glands. In this report we describe ongoing studies on the actions of TCDD on cultured human epidermal cells. This system has been established as an in vitro model for interfollicular epidermal hyperkeratinization. Treatment of newly confluent cultures with TCDD results in enhanced differentiation as judged by histologic examination of the cultures, a decrease in the number of basal proliferating cells, and an increase in the number of envelope competent (differentiating) cells and terminally differentiated cells with highly cross-linked cornified envelopes. Changes in the differentiation program are preceded by a decrease in epidermal growth factor (EGF) binding. The concentration dependence and stereospecificity for these responses suggest the involvement of the Ah receptor. We propose that TCDD modulates normal patterns of epidermal differentiation through direct actions on proliferating basal cells, modulating the responsiveness of these cells to growth factors such as EGF.

Cell Differentiation↗
PubMed1985

Toxicity of chlorinated aromatic compounds in animals and humans: in vitro approaches to toxic mechanisms and risk assessment.

Human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and chlorinated analogs commonly results in pathological changes in the skin and its appendages characterized by thickening of the epidermis (acanthosis), hyperkeratosis and squamous metaplasia of the epithelial lining of the sebaceous glands. Acneform lesions (chloracne) develop as hair follicles dilate and fill with keratin and sebaceous glands become cystic. In animal models it has been found that the chloracneogenic potential of the halogenated aromatic compounds examined corresponds with the relative affinity of these same compounds for the cytosolic TCDD receptor. This receptor controls the coordinate expression of a number of inducible enzyme activities and in certain cell targets can alter normal programs of proliferation and differentiation. In this report we describe some of our ongoing studies on the mechanisms of action of TCDD in normal human epidermal cells and squamous cell carcinoma (SCC) lines. These systems permit detailed investigation of the molecular and biochemical events underlying pathologic changes in the skin and offer the potential of establishing a risk assessment model for halogenated aromatic compounds by using human target cells.

Animals↗
PubMed1984

Isolation of bluetongue and related viruses from Culicoides spp. in the Sudan.

Infection of domestic ruminants with bluetongue virus (BTV) is widespread in the Sudan but there are no records of vector species of Culicoides in that country. Therefore, light-trap collections of Culicoides for virus isolation procedures were made in the Khartoum and Um Benein areas of the Sudan during September-October 1982. Two virus isolates were made from pools of unengorged, female Culicoides. An isolate from a pool of C. kingi (schultzei gp) is a member of the Epizootic Haemorrhagic Disease (EHD) serogroup. The other isolate from a pool of C. imicola, a known BTV vector in other parts of Africa, is type-5 BTV. In laboratory experiments, the North American vector of BTV, C. variipennis, supported replication of both Sudanese isolates to a high titre and transmission occurred after 10 days' incubation. This paper records the first isolation in the Sudan of arboviruses from Culicoides, with the identification of a BTV serotype and the presence of a member of the EHD (genus orbivirus, family Reoviridae) serogroup.

Animals↗
PubMed1983

The variability of blood pressure measurements in children.

This study examined the sources and amount of variation present in the blood pressures of 99 third grade children, using data collected from three repeated measurements made on three separate visits. The results highlight factors to consider when planning or evaluating studies designed to relate children's blood pressure levels to environmental conditions. Factors include variability both between and within children by visit and between observers; periodic restandardization of observers during the course of a study is desirable.

Analysis of Variance↗
PubMed1981

Tumor-promoting phorbol esters affect production of prolactin and growth hormone by rat pituitary cells.

GH4C1 cells are strain of rat pituitary cells which synthesize and secrete both PRL and GH. Phorbol esters, which are potent tumor promoters in mouse skin and have diverse actions in a variety of cell and tissue systems, were found to alter hormone production by GH4C1 cells. 12-O-Tetradecanoylphorbol-13-acetate (TPA), the most potent phorbol ester, stimulated both PRL synthesis and release. The synthesis of PRL was stimulated 2.3- to 6.2-fold over control values after 3 days of treatment; the ED50 for TPA was 8.9 +/- 2.1 nM (5.5 +/- 1.3 ng/ml). The release of stored PRL was stimulated within 10 min of the addition of 100 ng/ml TPA to the culture medium. Maximum stimulation of release was 1.3- to 2.3-fold over control, and the ED50 for TPA was 13.2 +/- 2.3 nM (8.1 +/- 1.4 ng/ml). Another tumor-promoting phorbol ester, phorbol 12,13-didecanoate (PDD), stimulated PRL synthesis and release to the same maximum extent at TPA, but two biologically inactive compounds, 4 alpha-PDD and phorbol, had no effect. The stimulation of PRL release by TPA was a Ca++-dependent process; Co++, a competitive antagonist of Ca++, at 2.0 mM blocked completely the stimulation of PRL release by 100 ng/ml TPA, and this block was overcome by 2.0 mM Ca++, but not by 2.0 mM Mg++. Although phorbol esters stimulate prostaglandin (PG) synthesis in certain other cells types, PGs were not required for TPA action in GH4C1 cells. Indomethacin, a PG cyclooxygenase inhibitor, at 200 ng/ml did not inhibit the stimulation of PRL synthesis and release by TPA. Furthermore, there was no detectable (less than 50 pg/ml) PGE2 or PGF2 alpha in the medium of control or TPA-treated cells. In GH3 cells, a related cell strain, TPA (100 ng/ml) decreased GH production in both control and hydrocortisone-stimulated cells to 35% of untreated control values after 3 days of incubation. TPA also altered cell morphology, but had little or no effect on cell growth. We conclude that GH cells provide a useful system to study the mechanisms of phorbol ester action on differentiated functions.

Animals↗
PubMed1980

Surgical manifestations and results of treatment of pulmonary coccidioidomycosis.

Fifty consecutive patients with pulmonary coccidioidomycosis undergoing operation in an eight-year period were analyzed with regard to clinical and roentgenographic indications, surgical procedure, complications, and recurrence. Surgical indications could be divided into operation necessary primarily for diagnosis (22 out of 50, 44%) and operation because of suspected residual complications of coccidioidomycosis requiring therapy (28 out of 50, 56%). Of 16 patients with solitary nodules, 2 had lobectomy and 14 had wedge resection with no recurrence. Of 24 patients with coccidioidomycosis cavities, 14 underwent lobectomy and 10 had lesser resections, with three recurrences. Results indicate that (1) resection for primary pulmonary coccidioidomycosis for both diagnosis and therapy is associated with low perioperative risk, (2) routine administration of amphotericin is not indicated, (3) skin tests, serological study, bronchoscopy, and mediastinoscopy may not be diagnostic, and (4) lobectomy is not necessarily indicated since lesser resections are associated with equally low recurrence and complications rates.

Coccidioidomycosis↗
PubMed1977

Preliminary report of the lung cancer detection program in New York.

The early lung cancer detection program in New York is described, and preliminary prevalence rate data are reported. Cigarette-smoking men over the age of 45, who are considered at high risk, are encouraged to enroll in the program and, to date, 6,612 have done so. These men receive PA and lateral chest x-rays annually, while a randomly selected sub-population of about half also have sputum cytology every four months. A controlled study of sputum cytology as an adjunct to the chest x-ray is now in progress. There were 15 cases of late lung cancer (pathologic stages II and III) detected at the initial examination, and 11 early cases (pathologic stages O and I). In the population of 3,387 men who had x-rays alone there were three early lung cancers detected; in the population of 3,225 men who had both examinations four early cancers were detected by x-ray and four by cytology. In addition, three cases of larynx cancer were detected by cytology. The early lung cancers detected by x-ray were peripheral and most were bronchiolar or adenocarcinoma; the early cancers detected by cytology were central epidermoid carcinoma of major bronchi. No early carcinomas were detected by both techniques. These findings suggest that a combination of chest x-rays and sputum cytology can be more effective than either one alone in detecting early lung cancer.

Age Factors↗